While both, vesicle-associated membrane protein 2 (VAMP2) and α -synuclein have been extensively studied, this study reveals a novel, unexpected role for their interaction. α-synuclein is a small intrinsically disordered protein which is involved in neurodegeneration. Being linked to synucleinopathies such as Parkinson’s disease and Lewy body dementia α-synuclein has attracted a lot of interest. This work from the Lautenschlager lab now shows that VAMP2, a SNARE complex protein situated at synaptic vesicles, regulates phase separation of α-synuclein, allowing it to form highly concentrated protein droplets, which cluster vesicles and protein partners. This underlines a new biological mechanism to understand α-synuclein’s role in health and disease.
Thanks goes to Aishwarya Agarwal and Aswathy Chandran who co-author this paper, and to the collaborations within the CIMR who contributed NMR studies and beautiful correlative light electron microscopy.
Please have a peek, out as back-to-back publication in Nature Cell Biology:
https://www.nature.com/articles/s41556-024-01451-6 and https://www.nature.com/articles/s41556-024-01456-1
Thanks again to the Royal Society, the Leverhulme Trust and the Addenbrooke’s Charitable Trust who have supported this work.